The use of oral antibiotics and mechanical bowel preparation in elective colorectal resection for the reduction of surgical site infection.

Surgical site infection (SSI) is a major cause of morbidity following elective colorectal resection worldwide. Reduction in SSI rates can be achieved with the use of SSI reduction bundles. Debate about the role of mechanical bowel preparation and oral antibiotics (MOAB) in reducing SSI has persisted over decades with considerable variation in international practice. This article summarises the arguments for and against the routine use of MOAB in the elective setting, highlighting the areas of controversy and evidence gaps and provides pragmatic suggestions for colorectal practice.This topical debate paper was commissioned by the President and Executive of the Association of Coloproctology of Great Britain and Ireland. ACPGBI also funded the open access publication fee. The authors would like to thank Ms J Pipe for her comments from the patient perspective and Miss N Fearnhead for her support in developing this debate article

Metabolic responses to the acute ingestion of two commercially available carbonated beverages: A pilot study

<p>Abstract</p> <p>Background</p> <p>The purpose of this placebo-controlled, double-blind cross-over study was to compare the effects of two commercially available soft drinks on metabolic rate.</p> <p>Methods</p> <p>After giving informed consent, twenty healthy men and women were randomly assigned to ingest 12 ounces of Celsius™ and, on a separate day, 12 ounces of Diet Coke®. All subjects completed both trials using a randomized, counterbalanced design. Metabolic rate (via indirect calorimetry) and substrate oxidation (via respiratory exchange ratio) were measured at baseline (pre-ingestion) and at the end of each hour for 3 hours post-ingestion.</p> <p>Results</p> <p>Two-way ANOVA revealed a significant interaction (p < 0.001) between trials in metabolic rate. Scheffe post-hoc testing indicated that metabolic rate increased by 13.8% (+ 0.6 L/min, p < 0.001) 1 hr post, 14.4% (+0.63 L/min, p < 0.001) 2 hr post, and 8.5% (+0.37 L/min, p < 0.004) 3 hr post Celsius™ ingestion. In contrast, small (~4–6%) but statistically insignificant increases in metabolic rate were noted following Diet Coke^®ingestion. No differences in respiratory exchange ratio were noted between trials.</p> <p>Conclusion</p> <p>These preliminary findings indicate Celsius™ has thermogenic properties when ingested acutely. The effects of repeated, chronic ingestion of Celsius™ on body composition are unknown at this time.</p

Intravenous iron is non-inferior to oral iron regarding cell growth and iron metabolism in colorectal cancer associated with iron-deficiency anaemia

© 2021 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1038/s41598-021-93155-2Oral iron promotes intestinal tumourigenesis in animal models. In humans, expression of iron transport proteins are altered in colorectal cancer. This study examined whether the route of iron therapy alters iron transport and tumour growth. Colorectal adenocarcinoma patients with pre-operative iron deficiency anaemia received oral ferrous sulphate (n = 15), or intravenous ferric carboxymaltose (n = 15). Paired (normal and tumour tissues) samples were compared for expression of iron loading, iron transporters, proliferation, apoptosis and Wnt signalling using immunohistochemistry and RT-PCR. Iron loading was increased in tumour and distributed to the stroma in intravenous treatment and to the epithelium in oral treatment. Protein and mRNA expression of proliferation and iron transporters were increased in tumours compared to normal tissues but there were no significant differences between the treatment groups. However, intravenous iron treatment reduced ferritin mRNA levels in tumours and replenished body iron stores. Iron distribution to non-epithelial cells in intravenous iron suggests that iron is less bioavailable to tumour cells. Therefore, intravenous iron may be a better option in the treatment of colorectal cancer patients with iron deficiency anaemia due to its efficiency in replenishing iron levels while its effect on proliferation and iron metabolism is similar to that of oral iron treatment.Published versio

The contribution of Swiss scientists to the assessment of energy metabolism

Although Switzerland is considered a small country, it has its share in discoveries, inventions and developments for the assessment of energy metabolism. This includes seminal contributions to respiratory and metabolic physiology and to devices for measuring energy expenditure by direct and indirect calorimetry in vivo in humans and small animals (as well as in vitro in organs/tissues), for the purpose of evaluating the basic nutritional requirements. A strong momentum came during World War II when it was necessary to evaluate the energy requirements of soldiers protecting the country by assessing their energy expenditure, as well as to determine the nutritional needs of the Swiss civil population in time of war when food rationing was necessary to ensure national neutrality and independence. A further impetus came in the 1970s at the start of the obesity epidemics, toward a better understanding of the metabolic basis of obesity, ranging from the development of whole-body concepts to molecular mechanisms. In a trip down memory lane, this review focuses on some of the earlier leading Swiss scientists who have contributed to a better understanding of the field

Energy expenditure during overfeeding

The large inter-individual variation in weight gain during standardized overfeeding together with a weight gain that is often less than theoretically calculated from the energy excess suggest that there are differences between persons in the capacity to regulate energy expenditure and hence metabolic efficiency. Adaptive thermogenesis is defined as the regulated production of heat in response to environmental changes in temperature and diet, resulting in metabolic inefficiency. The question is whether adaptive thermogenesis can be identified in overfeeding experiments. From the numerous human overfeeding experiments we selected those studies that applied suitable protocols and measurement techniques. Five studies claimed to have found evidence for adaptive thermogenesis based on weight gains smaller than expected or unaccounted increases in thermogenesis above obligatory costs. Results from the other 11 studies suggest there is no adaptive thermogenesis as weight gains were proportional to the amount of overfeeding and the increased thermogenesis was associated with theoretical costs of an increased body size and a larger food intake. These results show that in humans, evidence for adaptive thermogenesis is still inconsistent. However, they do not rule out the existence, but emphasize that if present, adaptive changes in energy expenditure may be too small to measure considering measurement errors, errors in assumptions made and small (day-to-day) differences in physical activity. In addition, it is not clear in which component or components of total energy expenditure adaptive changes can occur and whether components can overlap due to measurement limitations

Determining the neurotransmitter concentration profile at active synapses

Establishing the temporal and concentration profiles of neurotransmitters during synaptic release is an essential step towards understanding the basic properties of inter-neuronal communication in the central nervous system. A variety of ingenious attempts has been made to gain insights into this process, but the general inaccessibility of central synapses, intrinsic limitations of the techniques used, and natural variety of different synaptic environments have hindered a comprehensive description of this fundamental phenomenon. Here, we describe a number of experimental and theoretical findings that has been instrumental for advancing our knowledge of various features of neurotransmitter release, as well as newly developed tools that could overcome some limits of traditional pharmacological approaches and bring new impetus to the description of the complex mechanisms of synaptic transmission

Pathogenic NR2F1 variants cause a developmental ocular phenotype recapitulated in a mutant mouse model

Pathogenic NR2F1 variants cause a rare autosomal dominant neurodevelopmental disorder referred to as the Bosch-Boonstra-Schaaf Optic Atrophy Syndrome. Although visual loss is a prominent feature seen in affected individuals, the molecular and cellular mechanisms contributing to visual impairment are still poorly characterized. We conducted a deep phenotyping study on a cohort of 22 individuals carrying pathogenic NR2F1 variants to document the neurodevelopmental and ophthalmological manifestations, in particular the structural and functional changes within the retina and the optic nerve, which have not been detailed previously. The visual impairment became apparent in early childhood with small and/or tilted hypoplastic optic nerves observed in 10 cases. High-resolution optical coherence tomography imaging confirmed significant loss of retinal ganglion cells with thinning of the ganglion cell layer, consistent with electrophysiological evidence of retinal ganglion cells dysfunction. Interestingly, for those individuals with available longitudinal ophthalmological data, there was no significant deterioration in visual function during the period of follow-up. Diffusion tensor imaging tractography studies showed defective connections and disorganization of the extracortical visual pathways. To further investigate how pathogenic NR2F1 variants impact on retinal and optic nerve development, we took advantage of an Nr2f1 mutant mouse disease model. Abnormal retinogenesis in early stages of development was observed in Nr2f1 mutant mice with decreased retinal ganglion cell density and disruption of retinal ganglion cell axonal guidance from the neural retina into the optic stalk, accounting for the development of optic nerve hypoplasia. The mutant mice showed significantly reduced visual acuity based on electrophysiological parameters with marked conduction delay and decreased amplitude of the recordings in the superficial layers of the visual cortex. The clinical observations in our study cohort, supported by the mouse data, suggest an early neurodevelopmental origin for the retinal and optic nerve head defects caused by NR2F1 pathogenic variants, resulting in congenital vision loss that seems to be non-progressive. We propose NR2F1 as a major gene that orchestrates early retinal and optic nerve head development, playing a key role in the maturation of the visual system

The use of digital photographs for the diagnosis of hand osteoarthritis: the AGES-Reykjavik study

<p>Abstract</p> <p>Background</p> <p>The objective of the study was to standardize a method using digital photographs to diagnose and grade hand osteoarthritis (HOA), to compare it with radiographs and clinical examination with regard to prevalence and relation to symptoms, and finally to construct a simple shortened version suitable for use in very large studies, where a global estimate may be preferable.</p> <p>Methods</p> <p>High quality photographs with standard distance and hand positioning were analysed for the presence of HOA and subsequently compared with standard radiographs and clinical examination in 381 random participants in the AGES-Reykjavik Study, a large population study. The mean age of the participants was 76 years.</p> <p>Results</p> <p>Using the photographic method, the most commonly affected joints were the second DIP joints followed by the third DIP joints and second and third PIP joints. Both interobserver (ICC = 0.83) and intraobserver reading agreements (ICC = 0.89) were acceptable. On comparison with radiography and clinical examination, aggregate scores were significantly correlated (R_s0.35-0.69), more so in females (R_s0.53-0.72) than males. Hand pain in males showed very little association with HOA findings by the three methods but all methods showed a comparable moderate association with hand pain in females. The performance of photography in predicting pain on most days for at least a month in females was comparable to that of radiography and clinical examination (AUC 0.63 <it>p </it>= 0.004). Analysis of intermittent pain yielded similar results for in the DIP and PIP joints (OR 3.2-3.3, <it>p </it>< 0.01), but for the CMC1 joints, both radiography (OR 9.0, <it>p </it>< 0.0001), and clinical examination (OR 9.8, <it>p </it>< 0.0001), had higher predictive odds ratios for pain than photography (OR 3.6, <it>p </it>< 0.0001)., A shortened, rapidly performed form of reading photographs also showed a high degree of correlation with the other methods (R_s0.56-0.82).</p> <p>Conclusion</p> <p>High quality hand photographs can be used to diagnose and grade hand osteoarthritis. The method has the advantage of being inexpensive and easy to perform. By using a slightly simplified method of reading, it appears to be highly suitable for use in large studies.</p

The Dopamine Augmenter L-DOPA Does Not Affect Positive Mood in Healthy Human Volunteers

Dopamine neurotransmission influences approach toward rewards and reward-related cues. The best cited interpretation of this effect proposes that dopamine mediates the pleasure that commonly accompanies reward. This hypothesis has received support in some animal models and a few studies in humans. However, direct assessments of the effect of transiently increasing dopamine neurotransmission have been largely limited to the use of psychostimulant drugs, which elevate brain levels of multiple neurotransmitters in addition to dopamine. In the present study we tested the effect of more selectively elevating dopamine neurotransmission, as produced by administration of the immediate dopamine precursor, L-DOPA (0, 100/25, 200/50 mg, Sinemet), in healthy human volunteers. Neither dose altered positive mood. The results suggest that dopamine neurotransmission does not directly influence positive mood in humans